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Cited by 213Neuroendocrine regulation and behaviorNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Effective modulation of male aggression through lateral septum to medial hypothalamus projection

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Wong, Li Chin, Wang, Li, D’Amour, James A., Yumita, Tomohiro, Chen, Genghe, Yamaguchi, Takashi, Chang, Brian C., Bernstein, Hannah +4 more·2016·Current Biology
DOI 10.1016/j.cub.2015.12.065PMC PMC4783202
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Abstract

Aggression is a prevalent behavior in the animal kingdom that is used to settle competition for limited resources. Given the high risk associated with fighting, the central nervous system has evolved an active mechanism to modulate its expression. Lesioning the lateral septum (LS) is known to cause "septal rage," a phenotype characterized by a dramatic increase in the frequency of attacks. To understand the circuit mechanism of LS-mediated modulation of aggression, we examined the influence of LS input on the cells in and around the ventrolateral part of the ventromedial hypothalamus (VMHvl)-a region required for male mouse aggression. We found that the inputs from the LS inhibited the attack-excited cells but surprisingly increased the overall activity of attack-inhibited cells. Furthermore, optogenetic activation of the projection from LS cells to the VMHvl terminated ongoing attacks immediately but had little effect on mounting. Thus, LS projection to the ventromedial hypothalamic area represents an effective pathway for suppressing male aggression.

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  1. [3]Goodson JL Evans AK Soma KK 2005 Neural responses to aggressive challenge correlate with behavior in nonbreeding sparrows Neuroreport 16 1719 1723 16189485 PMC2596666
  2. [4]Zeman W King FA 1958 Tumors of the septum pellucidum and adjacent structures with abnormal affective behavior: an anterior midline structure syndrome The Journal of nervous and mental disease 127 490 502 13621217
  3. [5]Albert DJ Chew GL 1980 The septal forebrain and the inhibitory modulation of attack and defense in the rat. A review Behav Neural Biol 30 357 388 7013753
  4. [6]Slotnick BM McMullen MF Fleischer S 1973 Changes in emotionality following destruction of the septal area in albino mice Brain Behav Evol 8 241 252 4798640
  5. [7]Potegal M Blau A Glusman M 1981 Effects of anteroventral septal lesions on intraspecific aggression in male hamsters Physiol Behav 26 407 412 7195593
  6. [8]McDonald MM Markham CM Norvelle A Albers HE Huhman KL 2012 GABAA receptor activation in the lateral septum reduces the expression of conditioned defeat and increases aggression in Syrian hamsters Brain Res 1439 27 33 22265703 PMC3273572
  7. [9]Lee G Gammie SC 2009 GABA(A) receptor signaling in the lateral septum regulates maternal aggression in mice Behav Neurosci 123 1169 1177 20001101 PMC2829870
  8. [10]Ramirez JM Salas C Portavella M 1988 Offense and defense after lateral septal lesions in Columba livia Int J Neurosci 41 241 250 3182182
  9. [11]Goodson JL Eibach R Sakata J Adkins-Regan E 1999 Effect of septal lesions on male song and aggression in the colonial zebra finch (Taeniopygia guttata) and the territorial field sparrow (Spizella pusilla) Behav Brain Res 98 167 180 10210532
  10. [12]Siegel A Skog D 1970 Effects of electrical stimulation of the septum upon attack behavior elicited from the hypothalamus in the cat Brain Res 23 371 380 5529465
  11. [13]Potegal M Blau A Glusman M 1981 Inhibition of Intraspecific Aggression in Male Hamsters by Septal Stimulation Physiol Psychol 9 213 218 7195593
  12. [14]Risold PY Swanson LW 1997 Connections of the rat lateral septal complex Brain Res Brain Res Rev 24 115 195 9385454
  13. [15]Blume HW Pittman QJ Lafontaine S Renaud LP 1982 Lateral septum-medial hypothalamic connections: an electrophysiological study in the rat Neuroscience 7 2783 2792 7155352
  14. [16]Lammers JH Kruk MR Meelis W van der Poel AM 1988 Hypothalamic substrates for brain stimulation-induced attack, teeth-chattering and social grooming in the rat Brain Res 449 311 327 3395851
  15. [17]Lipp HP Hunsperger RW 1978 Threat, attack and flight elicited by electrical stimulation of the ventromedial hypothalamus of the marmoset monkey Callithrix jacchus Brain Behav Evol 15 260 293 100172
  16. [18]Siegel A Pott CB 1988 Neural Substrates of Aggression and Flight in the Cat Prog Neurobiol 31 261 283 3045882
  17. [19]Siegel A Roeling TAP Gregg TR Kruk MR 1999 Neuropharmacology of brain-stimulation-evoked aggression Neurosci Biobehav R 23 359 389 9989425
  18. [21]Yang CF Chiang MC Gray DC Prabhakaran M Alvarado M Juntti SA Unger EK Wells JA Shah NM 2013 Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males Cell 153 896 909 23663785 PMC3767768
  19. [22]Lee H Kim DW Remedios R Anthony TE Chang A Madisen L Zeng H Anderson DJ 2014 Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus Nature 509 627 632 24739975 PMC4098836
  20. [23]Falkner AL Dollar P Perona P Anderson DJ Lin D 2014 Decoding ventromedial hypothalamic neural activity during male mouse aggression J Neurosci 34 5971 5984 24760856 PMC3996217
  21. [24]Millhouse OE 1973 The organization of the ventromedial hypothalamic nucleus Brain Res 55 71 87 4713193
  22. [25]Millhouse OE 1973 Certain Ventromedial Hypothalamic Afferents Brain Res 55 89 105 4197323
  23. [26]Sheehan TP Chambers RA Russell DS 2004 Regulation of affect by the lateral septum: implications for neuropsychiatry Brain Res Brain Res Rev 46 71 117 15297155
  24. [28]Kita T Nishijo H Eifuku S Terasawa K Ono T 1995 Place and contingency differential responses of monkey septal neurons during conditional place-object discrimination J Neurosci 15 1683 1703 7891128 PMC6578137
  25. [29]Vong L Ye C Yang Z Choi B Chua S Jr Lowell BB 2011 Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons Neuron 71 142 154 21745644 PMC3134797
  26. [30]Zhao C Eisinger B Gammie SC 2013 Characterization of GABAergic neurons in the mouse lateral septum: a double fluorescence in situ hybridization and immunohistochemical study using tyramide signal amplification PloS one 8 e73750 23967349 PMC3742568
  27. [33]Brady JV Nauta WJ 1953 Subcortical mechanisms in emotional behavior: affective changes following septal forebrain lesions in the albino rat J Comp Physiol Psychol 46 339 346 13109048
  28. [34]Herman JP Cullinan WE 1997 Neurocircuitry of stress: Central control of the hypothalamo-pituitary-adrenocortical axis Trends in Neurosciences 20 78 84 9023876
  29. [35]Sodetz FJ Bunnell BN 1970 Septal ablation and the social behavior of the golden hamster Physiol Behav 5 79 88 5538529
  30. [36]Numan R 2000 The behavioral neuroscience of the septal region New York Springer
  31. [37]Mesic I Guzman YF Guedea AL Jovasevic V Corcoran KA Leaderbrand K Nishimori K Contractor A Radulovic J 2015 Double Dissociation of the Roles of Metabotropic Glutamate Receptor 5 and Oxytocin Receptor in Discrete Social Behaviors Neuropsychopharmacology PMC4538348 25824423
  32. [39]Hahn JD Swanson LW 2015 Connections of the juxtaventromedial region of the lateral hypothalamic area in the male rat Frontiers in systems neuroscience 9 PMC4445319 26074786
  33. [40]Canteras NS Simerly RB Swanson LW 1994 Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat J Comp Neurol 348 41 79 7814684
  34. [41]Kruk MR Vanderpoel AM Meelis W Hermans J Mostert PG Mos J Lohman AHM 1983 Discriminant-Analysis of the Localization of Aggression-Inducing Electrode Placements in the Hypothalamus of Male-Rats Brain Res 260 61 79 6681724
  35. [42]Robinson RB 2003 Hyperpolarization-activated cation currents: From molecules to physiological function Annu Rev Physiol 65 453 480 12471170
  36. [43]Qiu J Bosch MA Jamali K Xue C Kelly MJ Ronnekleiv OK 2006 Estrogen upregulates T-type calcium channels in the hypothalamus and pituitary J Neurosci 26 11072 11082 17065449 PMC6674650
  37. [44]Roux L Buzsaki G 2015 Tasks for inhibitory interneurons in intact brain circuits Neuropharmacology 88 10 23 25239808 PMC4254329
  38. [45]Dollar P Welinder P Perona P 2010 Cascaded Pose Regression IEEE Conference on Computer Vision and Pattern Recognition
  39. [46]Burgos-Artizzu XP Dollár P Lin D Anderson DJ Perona P 2012 Social Behavior Recognition in continuous videos IEEE Conference on Computer Vision and Pattern Recognition Providence Rhode Island

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Authors
Wong, L. C., Wang, L., D’Amour, J. A., Yumita, T., Chen, G., Yamaguchi, T., Chang, B. C., Bernstein, H., You, X., Feng, J. E., Froemke, R. C., & Lin, D.
Affiliations
  • New York University (US)
  • Nathan Kline Institute for Psychiatric Research (US)
  • NYU Langone Health (US)
Corresponding author
Lin, Dayu
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2016-03
Volume
26
Issue
5
Pages
593-604
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2015.12.065
PMC
PMC4783202
OpenAlex
W2254141494
Cited by
213
References
6
Citations by year
2026: 20 · 2025: 24 · 2024: 22 · 2023: 25 · 2022: 24 · 2021: 21 · 2020: 35 · 2019: 19 · 2018: 11 · 2017: 8 · 2016: 4
FWCI
22.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01MH101377)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
male aggression, lateral septum, ventromedial hypothalamus, optogenetic stimulation, aggression reduction, neural circuit modulation, mouse behavior
MeSH terms
Aggression, Animals, Hypothalamus, Middle, Male, Mice, Inbred C57BL, Septal Nuclei, Sexual Behavior, Animal, Mice, Optogenetics

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